rs765903345

Variant names:

• chr2-238328794-C-A
• rs765903345
• NM_015650.4:c.463C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-238328794-C-A
• chr2-238328794-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_015650.4(TRAF3IP1):​c.463C>A​(p.Arg155Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRAF3IP1 NM_015650.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.31
• Publications: 0 publications found

Genes affected

TRAF3IP1 (HGNC:17861): (TRAF3 interacting protein 1) The protein encoded by this gene interacts with TNF receptor-associated factor 3, tethering it to cytoskeletal microtubules. The encoded protein is also an inhibitor of the innate type I IFN response. Defects in this gene are a cause of Senior-Loken syndrome 9. [provided by RefSeq, Mar 2017]

TRAF3IP1 Gene-Disease associations (from GenCC):

• Senior-Loken syndrome 9

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• Senior-Loken syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• short rib-polydactyly syndrome, Majewski type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 2-238328794-C-A is Benign according to our data. Variant chr2-238328794-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2133734.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.31 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015650.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF3IP1	NM_015650.4	MANE Select	c.463C>A	p.Arg155Arg	synonymous	Exon 4 of 17	NP_056465.2
	TRAF3IP1	NM_001139490.1		c.463C>A	p.Arg155Arg	synonymous	Exon 4 of 15	NP_001132962.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRAF3IP1	ENST00000373327.5	TSL:1 MANE Select	c.463C>A	p.Arg155Arg	synonymous	Exon 4 of 17	ENSP00000362424.4
	TRAF3IP1	ENST00000391993.7	TSL:1	c.463C>A	p.Arg155Arg	synonymous	Exon 4 of 15	ENSP00000375851.3
	TRAF3IP1	ENST00000409739.2	TSL:3	n.*332C>A		non_coding_transcript_exon	Exon 4 of 5	ENSP00000386648.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.3
DANN	Benign	0.45
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs765903345; hg19: chr2-239237435;